Chromatin immunoprecipitation (ChIP) is a research tool that is used to identify DNA binding sites in the genome for a particular protein of interest. For this, DNA-binding proteins in living cells are reversibly crosslinked to the DNA to which they are bound. The chromatin-protein complexes are then captured using an antibody against the protein of interest. The chromatin-protein-antibody complexes generally are isolated by contact with an immobilized protein that binds antibodies. For example, protein A of Staphylococcus binds the Fc domain of antibodies. Thus, isolated protein A may be immobilized on a solid support and used to capture chromatin-protein-antibody complexes. Alternatively, heat-inactivated Staphylococcus cells in which protein A and other cell wall proteins have been fixed in place (i.e., Staph A cells) may be used to isolate the chromatin-protein-antibody complexes. Not only are Staph A cells much cheaper, but also they are better suited for isolating DNA bound by low abundance proteins due to their high protein A content.
One problem of using Staph A cells, however, is that the DNA-protein complexes isolated with Staph A cells may be contaminated with Staphylococcus DNA. In PCR or hybridization based applications (e.g., ChIP-on-chip) using sequence-specific primers or probes, the contaminating Staphylococcus DNA does not interfere with analysis of the isolated DNA of interest. In DNA sequencing applications (e.g., ChIP-Seq) or other sequence-independent methods, however, the contaminating Staphylococcus DNA does interfere with the analysis. Although DNA blocking procedures such as incubating Staph A cells with agents such as herring sperm DNA and bovine serum albumin have been developed, there still exists a need for more effective procedures for inactivating the chromosomal DNA of Staphylococcus cells such that it does not interfere with sequence-independent procedures (i.e., those requiring strand separation).